Recent studies dealing with the role of Clostridium perfringens enterotoxin in digestive disease have elucidated important and revealing information concerning the interaction of the enterotoxin with gut tissue and the structure and function of the gut. We have shown, for example, that the enterotoxin causes diarrhea, the major symptom of perfringens food poisoning, by inducing net luminal accumulation of electrolytes and fluid in the ileum of animal models. More definitive studies of this model system have revealed that the enterotoxin inhibits glucose transport, alters tissue metabolic activity, and causes severe changes in gut tissue morphology and epithelial cell membrane structure. These findings distinguish the action of this enterotoxin from known actions of other enterotoxins. The proposed research will 1) provide a new and highly sensitive assay system for biological activity of the enterotoxin and 2) develop a versatile tissue culture system for studying the activity of the enterotoxin. 3) It will further elucidate the mechanism by which unique enterotoxin causes functional and structural alterations of the intestine. This will be accomplished through experiments done with whole animals, isolated cell systems from the intestine of the animals, and established cell cultures. This research will also 4) provide a tool for studying and understanding intestinal epithelial cell membrane structure, configuration, and function through analysis of the interactions and alterations resulting from the biological activity of the enterotoxin.